nervous system
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• adult homozygotes display no significant differences in overall cytoarchitecture and nerve cell density of the cerebellum and other brain regions relative to wild-type littermates
• in particular, the density and ultrastructure of synapses in the molecular layer of mutant cerebella is indistinguishable from that of wild-type littermates
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• homozygotes display impaired synaptic transmission at parallel fiber-Purkinje cell synapses in the cerebellum
• however, the frequency and amplitude of spontaneous excitatory postsynaptic responses (EPSCs) of mutant Purkinje cells remain normal
• in addition, the frequency, amplitude, and rise time of spontaneous miniature inhibitory postsynaptic responses (IPSCs) of mutant Purkinje cells remain unaffected, suggesting normal synaptic vesicle priming at GABAergic synapses terminating on Purkinje cells
• amplitudes of successive EPSCs plotted as a function of stimulus number during repetitive stimulation at 14 Hz indicate that neither wild-type nor mutant Purkinje cells display synaptic depression at this stimulation frequency
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• at interstimulus intervals of up to 200 msec, cerebellar slices from P18-P21 homozygotes show a significant increase in paired-pulse facilitation at parallel fiber-Purkinje cell synapses, suggesting a decrease in transmitter release probability from mutant synapses relative to wild-type controls
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behavior/neurological
• in a 22 session motor learning paradigm, homozygotes display a significant deficit in motor learning at higher rotation speeds, whereas wild-type mice achieve a significantly higher rotation speed than mutants from the 11th session onward
• however, both genotypes improve similarly with training at lower rotation speeds, and no significant differences are noted in the falling latency of naive wild-type and mutant mice at a rotating speed of 40 rpm
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